Supplementary Material: Increased Emulsion Stability for Reverse Y-Shaped Sugar Based

Supplementary Material: Increased emulsion stability for reverse Y-shaped sugar based surfactants

Tammar Hussein Ali, Hairul Anuar Bin Tajuddin, Rusnah Syahila Duali Hussen, Thorsten Heidelberg

Increased emulsion stability for reverse Y-shaped sugar based surfactants

Tammar Hussein Ali, Hairul Anuar Bin Tajuddin, Rusnah Syahila Duali Hussen, Thorsten Heidelberg

Chemistry Department, Faculty of Science, University of Malaya, 50603 Kuala Lumpur,

Malaysia;

Supplementary Material

Experimental Procedures & Analytical Data

2-Dihexylamino-ethyl 2,3,4,6-tetra-O-acetyl--D-glucopyranoside (1)

To a mixture of 2-bromoethyl 2,3,4,6-tetra-O-acetyl--D-glucopyranoside18[[1]](4.0 g, 8.8mmol)and K2CO3 (1.8 g, 13 mmol) in acetonitrile (50 mL), dihexyl amine11 (1.9 mL, 8.2mmol) was added. The reaction mixture was refluxed overnight, and then filtrate and the solvent was evaporated.The residue was taken up in water and extracted with CH2Cl2 three times. The combined organic phase was washed with brine water, and then dried over MgSO4and concentratedon a rotary evaporator. The crude product was purified by column chromatography using hexane: ethyl acetate (3:1) to obtain 1 as brown syrup (3.0 g, 61%). 1H NMR (CDCl3) δ= 5.19 (dd~t, H-3); 5.07 (dd~t, H-4); 4.96 (dd, H-2); 4.57 (d, H-1); 4.26 (dd, H6a); 4.14 (dd, H-6b); 3.97-3.91 (m, H-5); 3.75- 3.68 (m,2H, OCH2); 2.79- 2.74 (m, CH2N); 2.53 (t, 4H, N(CH2)2); 2.08, 2.04, 2.02, 2.00 (4 s, 12H, Ac); 1.46 (mc, 4H, -CH2); 1.28 (mc, 12H, bulk-CH2); 0.89 (t, 6H, CH3); 3J1,2 = 8.0, 3J2,3 = 9.0, 3J3,4 = 9.5, 3J4,5 = 9.5, 3J5, 6a = 4.0,
2J6 = 11.8 Hz. 13C NMR (CDCl3) δ= 170.65, 170.28, 169.39, 169.24 (CO); 100.81 (C-1); 72.91 (C-4); 71.75 (C-2); 71.31 (C-3); 68.45 (C-5); 68.34 (OCH2); 61.99 (C-6); 54.77 (N(CH2)2); 53.33 (CH2N); 31.80 (ω-2); 27.16, 27.10 (-CH2); 22.64 (ω-1); 20.70, 20.66, 20.58, 20.57 (Ac); 14.04 (CH3).

2-(Dihexylamino-ethyl -D-glucopyranoside (2)

1 (2.9 g, 5.3 mmol) was reacted according to general procedure II to produce 2 (1.9 g,91%). as brown syrup. 1H NMR (DMSO-d6) δ= 4.18 (d, H-1, 3J1,2 = 7.5 Hz) 3.94 (dd~bt, H-3); 3.80- 3.60 (m, 2H, OCH2); 3.22- 2.95 (m, 7H, H-4, H-2, H-5, H-6, CH2N); 2.81 (bt, 4H, N(CH2)2); 1.51 (m, 4H, 2x -CH2); 1.25 (mc, 12H, bulk-CH2); 0.85 (t, 6H, CH3). 13C NMR (DMSO-d6) δ= 103.33 (C-1); 77.33 (C-4); 76.92 (C-2); 73.82 (C-3); 70.51 (C-5); 64.85 (OCH2); 61.56 (C-6); 53.26 (N(CH2)2); 52.37 (CH2N); 31.34 (ω-2); 26.49, 26.45 (-CH2); 22.42 (ω-1); 14.21 (CH3).

3,5-Bis(hexyloxy)benzyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside (3)

-Glucose pentaacetate 17(3.0 g, 7.8 mmol) and 15 (2.0 g, 6.5 mmol) were dissolved in CH2Cl2 (60 mL) dichloromethane and treated with BF3xEt2O (3.0 mL, 24 mmol). The reaction was stirred at room temperature for 3 hours and then washed with NaHCO3 aq and dried over MgSO4. The solvent was evaporated and the crude product purified by column chromatography using hexane: ethyl acetate (3:1) to provide 3as colorless solid. (4.0 g, 82%). 1H NMR (CDCl3) δ= 6.41 (s, 2H, CH-benzene); 6.38 (s, CH-benzene); 5.17 (dd~t, H-3); 5.10 (dd~t, H-4); 5.06 (dd, H-2);; 4.82 (d, Bn-A); 4.54 (d, Bn-B); 4.54 (d, H-1); 4.27 (dd, H-6a); 4.14 (dd, H-6b); 3.92 (t, 4H, OCH2); 3.66 (ddd, H-5); 2.10, 2.02, 2.01, 1.98 (4s, 12H, CH3CO); 1.75/ 1.44 (2x p, 4H, CH2); 1.34- 1.25 (m, 12H, bulk-CH2); 0.90 (t, 6H, CH3); 3J1,2 = 8.0, 3J2,,3 = 9.0, 3J3,4 = 9.5, 3J4,5 = 9.5, 3J5,6a = 4.5, 3J5,6B = 2.0, 2J6 = 12.5, 2JBn = 12.5Hz. 13C NMR (CDCl3) δ= 170.61, 170.19, 169.35, 169.27 (CO); 160.43 (2x Cbenzene); 138.74 (Cbenzene); 106.09 (2x CHbenzene); 100.45 (CHbenzene); 99.08 (C1); 72.87 (C-4); 71.80 (C-2); 71.32 (C-3); 70.49 (Bn); 68.42 (C-5); 67.99 (2x CH2O); 61.92 (C-6); 31.54 (ω-2); 29.20 (CH2); 25.70 (-CH2); 22.60, 22.55 (ω-1); 20.66, 20.57, 20.53, 20.51 (Ac); 14.05, 13.96 (CH3).

3,5-Dihexyloxy-benzyl--D-glucopyranoside (4)

3 (4.0 g, 6.2 mmol) was reacted according to general procedure II to produce 4 (2.8 g, 95%) as white solid. 1H NMR (DMSO-d6) δ= 6.54 (s, 2x CH-benzene); 6.33 (s, CH-benzene); 4.73(d, Bn-A); 4.53 (d, Bn-B); 4.20 (d, H-1); 3.91 (t, 4H, 2x OCH2); 3.70 (dd~bd, H6a); 3.46 (dd, H-6b); 3.18- 3.06 (m, 3H, H-3, H-4, H-5), 3.04 (dd, H-2); 1.67 (p, 4H, 2x -CH2); 1.41-1.29 (m, 12H, bulk-CH2); 0.87 (mc, 6H, CH3).3J1,2 = 8.0, 3J2,3= 9.5,3J5,6a1.0, 3J5,6B = 5.0,2J6 = 12.0, 2JBn= 13.0 Hz. 13C NMR (DMSO-d6) δ= 160.20(2xCbenzene); 140.89 (Cbenzene); 106.02
(2x CHbenzene); 102.39 (C-1); 100.39 (CHbenzene); 77.38 (C4); 77.15 (C-2); 73.98 (C-3); 70.60 (C5); 69.63 (Bn); 67.86 (CH2O); 61.61 (C-6); 31.45 (ω-2); 29.12 (-CH2); 25.66 (CH2); 22.53 (ω1); 14.35 (CH3).

4-(Dihexylamino-methyl),1-[2-hydroxy,3-(-2,3,4,6-tetra-O-acetyl--D-glucopyranosyloxy)propyl]-1,2,3-triazole (5)

Sugar azide 22[[2]] (2.0 g, 4.5mmol) and propargyl 12 (1.1 g, 4.9 mmol) were coupled with CuCl (40 mg, 0.2 mmol) in MeOH according to the general procedure I to provide 5 (2.1 g, 70%) as a brown syrup. 1H NMR (CDCl3) δ= 8.20-7.43(m, triazole)*, 5.24/ 5.20 (2dd2t, H-3), 5.08 (dd~t, H-4), 5.00 (dd~bt, H-2), 4.63 (d, H-1), 4.50- 2.96 (14H, OCH2, H-6a,b, H-5 CHOH, CH2-triazole, N(CH2)2, CH2N), 2.17, 2.09, 2.03, 2.01 (4s, 12H, Ac), 1.88- 1.65 (m, 4H, 2x -CH2), 1.38- 1.25 (m, 12H, bulk-CH2), 0.93- 0.86 (m, 6H, CH3).3J 1,2 = 8.0, 3J 3,4 = 9.2, 3J 4,5 = 9.5 Hz.13C NMR (CDCl3) δ=170.84, 170.23, 169.82, 169.52 (CO), 134.26 (C-triazole), 130.02/130.04 (CH-triazole), 101.14/100.85 (C-1), 72.75 (C-4), 71.86/71.99 (C-2), 71.27/71.21 (C-3), 71.11 (OCH2), 68.35 (CHOH, C-5), 61.85 (C-6), 58.84 (NCH), 53.50 (CH2-triazole), 53.25(N(CH2)2), 31.18 (-2), 29.69 (bulk-CH2), 25.93 (-CH2), 22.42 (-1), 20.85, 20.79, 20.61 (Ac), 13.93, 13.89 (CH3).

4-(Dihexylamino-methyl)-1-[(2-hydroxy-3--D-glucopyranosyloxy)-propyl]-

1,2,3-triazole (6)

5 (2.0 g, 3.1 mmol) was reacted according to general procedure II to produce 6 (1.5 g, 96 %.) as brown syrup. 1H NMR (CD3OD) δ= 8.52-7.43 (m, triazole)*,4.62 (bs, H-1), 4.35(ddt, H3), 4.24 (mc, CHOH), 3.98-3.17(15H, H-2, H-4, OCH2, H-6a, H-6b, CH2, N(CH2)2, CH2N, H-5)with solvent peak, 1.88 (mc, 4H, -CH2), 1.43-1.30 (m, 12H, bulk-CH2), 0.97- 0.86 (m, 6H, CH3). 13C NMR (CD3OD) δ= 134.89 (C-triazole), 132.50 (CH-triazole), 103.30/103.19 (C-1), 76.68 (C-4), 76.55/76.50 (C-2), 73.73/73.65 (C-3), 70.62/70.51 (OCH2), 68.80/68.72 (CHOH, C-5), 61.30 (C-6), 57.97 (NCH), 52.99 (CH2-triazole), 52.10 (N(CH2)2), 30.94 (-2), 29.69 (-CH2), 25.87, 25.57 (-CH2), 22.14, 21.64 (-1), 12.89 (CH3).

* The inter-molecules H-bonding due to interaction of the glycerol hydroxyl group with the triazole gives rise to conformers, beside that the presence of diastereomers due to the racemic center of the glycerol at C-2 complicate the NMR analysis.

4-(3,5-Dihexyloxybenzoxymethyl),1-[2--(2,3,4,6-tetra-O-acetyl--D-glucopyranosyloxy)ethyl]-1,2,3triazole (7)

Sugar azide 19 (2.0 g, 4.4 mmol) and propargyl 16 (1.7 g, 4.9 mmol) were coupled with CuCl (40 mg, 0.2 mmol) in MeOH according to the general procedure I to provide 7 (2.6 g, 71%) as a brown syrup. 1H NMR (CDCl3) 7.63 (s, CH-triazole), 6.46 (bs, 2H, CH-benzene), 6.38 (bs, CH-benzene), 5.18 (dd~t, H-3), 5.07 (dd~t, H-4), 5.00 (dd, H-2), 4.64- 4.47 (m, 7H, OCH2, CH2N, CH2-benzyl, H-1), 4.24 (d, H-6a), 4.20(d, H-6b), 4.12/ 4.09 (2 s, 2HCH2O), 3.93 (t,4H, OCH2), 3.70 (ddd, H-5), 2.08, 2.02, 1.99, 1.96, (4s, 4x3H, Ac), 1.76 (p, 4H, -CH2), 1.45 (p, 4H, -CH2), 1.35- 1.33 (m, 8H, bulk-CH2), 0.90 (t, 6H, CH3); 3J1,2 = 8.0, 3J2,3 = 9.5,
3J3,4 = 9.0, 3J5, 6a = 4.5, 3J5, 6B = 7.5, 2J6 = 12.0Hz.13C NMR (CDCl3) 170.57, 170.08, 169.39, 169.36 (O), 160.40 (2x Cbenzene), 139.92 (Cbenzene), 139.63 (C-triazole), 126 (CH- triazole), 106.12 (2x CHbenzene), 100.68 (CHbenzene), 100.51 (C-1), 72.66 (CH2-benzyl), 72.48 (C-3), 71.98 (C-4), 70.89 (C-2), 68.21 (C-5), 68.03 (OCH2), 67.73 (OCH2-triazole), 63.48 (OCH2Ph), 61.70 (C-6), 50.0 (CH2N), 31.56 (ω-2), 29.22 (bulk-CH2), 25.71 (-CH2), 22.58 (ω-1), 20.70, 20.55, 20.48 (Ac), 14.02 (CH3).

4-(3,5-Dihexyloxy-benzoxymethy1,1[2-(-D-glucopyranosyloxy)-ethyl]-1,2,3-triazole (8)

7(2.6 g, 3.4 mmol) was reacted according to general procedure II to produce 8 (1.9 g, 95%.) as brown syrup. 1H NMR (CD3OD) 8.29 (bs, CH-triazole), 6.52 (bd, 2H, CH-benzene), 6.39 (bt, CH-benzene), 4.72 (t, 2 H, CH2N), 4.67 4.55 (2 s, 2×2 H, CH2OAr), 4.34 (d, H-1), 4.28 (ddd~dt,CH2O-A), 4.07 (ddd~dt, CH2O-B), 3.95 (t, 4H, -CH2), 3.89 (dd, H-6a), 3.66 (dd, H-6b), 3.37- 3.24 (m, 3H, H-3, H-4, H-5), 3.18 (dd, H-2), 1.76 (p, 4H, -CH2), 1.52- 1.45 (p, 4H, -CH2), 1.39-1.30 (m, 8H, bulk-CH2), 0.94 (t, 6H, CH3);3J1,2 = 8.0, 3J2,3= 9.0,
3J5,6a = 2.0, 2J6a,b = 5.0,2J6 = 12.0, 2JA,B = 12.0 Hz. 13C NMR (CD3OD) 160.45 (2x Cbenzene), 139.76 (Cbenzene), 139.63 (C-triazole), 126 (CH- triazole), 105.87 (2x CHbenzene), 103.14 (CHbenzene), 100.34 (C-1), 76.70 (C-3), 76.56 (C-4), 73.49 (C-2), 72.27 (CH2-benzyl), 70.11 (C5), 67.66 (2xOCH2), 67.35 (OCH2-triazole), 61.89 (OCH2), 61.27 (C-6), 51.10 (CH2N), 31.38 (ω-2), 28.98 (bulk-CH2), 25.74 (-CH2), 22.27 (ω-1), 12.97 (2x CH3).

2-N-propynyl-N,N-dihexyl amine (12)

To a stirred solution of dihexyl amine11 (3.0 mL, 13mmol) and K2CO3 (1.8 g, 13 mmol) in acetonitrile, propargyl bromide (80% w/w in toluene, 2.9 mL, 26 mmol) was added. The reaction mixture was refluxed at 70°C for overnight. The mixture was filtered, before the solvent was evaporated and the residue was extracted three times with CH2Cl2 against water. The combined organic phase was washed with brine and dried over MgSO4.Evaporation of the solvent furnished 12 as brown syrup, (2.7 g, yield 94%).1H NMR (CDCl3) δ= 4.68 (d, CH2N), J=2.47; 3.66- 3.51 (m, 4H, NCH2); 2.99 (t, CH-propargyl); 1.82 (p, 4H, -CH2); 1.32- 1.23 (m, 12H, bulk-CH2); 0.82 (t, 6H, CH3). 13C NMR (CDCl3) δ= 79.80 (C-propargyl); 75.62 (CHpropargyl); 59.98 (CH2N); 58.52 (N(CH2)2); 28.97 (bulk-CH2); 24.00 (-CH2); 20.36 (ω-1); 11.86 (CH3).

Methyl-3,5-bis(hexyloxy)benzoate(14)

1-bromohexane (7 mL, 50 mmol) was added to a stirred solution of methyl-3,5-dihydroxybenzoate [[3]] (4.0 g, 24 mmol) and K2CO3 (9.8 g, 71 mmol) in DMF (40 mL). The reaction mixture heated to 80 °C overnight before solid contents were filtered off and then the solvent was evaporated. The residue was taken up in water and extracted three times with CH2Cl2. The combined organic phases was washed with brine water, dried over MgSO4 andthen concentrate in a rotary evaporate to give14 as brown dark oil (7.2 g, 90%). 1H NMR (CDCl3) δ= 7.61 (s, 2H, CH-benzene); 6.63 (s, CH-benzene); 3.96 (t, 4H, OCH2); 1.77 (p, 4H,-CH2); 1.45 (p, 4H, CH2); 1.33 (bs, 8H, bulk-CH2); 0.90 (t, 6H, CH3). 13C NMR (CDCl3) δ= 166.99 (CO); 160.16 (2x Cbenzene); 131.82 (Cbenzene); 107.63 (2x CHbenzene); 106.59 (CHbenzene); 68.32 (2xOCH2); 31.54 (ω-2); 29.14 (-CH2); 25.67 (-CH2); 22.58 (ω-1); 14.00 (2x CH3).

3,5-Bis(hexyloxy)benzyl alcohol (15)

Lithium aluminium hydride (0.5 g, 13.51 mmol) was added to a stirred solution of methyl-3,5-bis(hexyloxy)benzoate 14(3.0 g, 8.9 mmol) in anhydrous THF (100 mL) at 10 ° C. The reaction mixture wasallowed to warm to room temperature and stirred for overnight. Water (0.5mL) was added slowly to stop the reaction, followed byNaOH aq. (1 mL, 10%) and additional water (2 mL). The reaction mixture was left to stir for around 30 min when the suspended solids have turned white. The solids were filtered off and subsequently washed with CH2Cl2.The filtrate was dried over MgSO4 and concentrate using a rotary evaporatorto give 15 as green dark oil (2.2 g, 80%). 1H NMR (CDCl3) δ= 6.48 (d, 2x CH-benzene), J= 2.48; 6.36 (t,CH-benzene), J= 2.28; 4.59 (s, CH2-benzyl); 3.92 (t, 4H, OCH2); 1.75 (p, 4H, -CH2); 1.44 (p,4H, CH2); 1.34 - 1.30 (m, 8H, bulk-CH2); 0.90 (t, 6H, CH3). 13C NMR (CDCl3) δ= 160.51 (2xCbenzene); 143.28 (Cbenzene); 105.06 (2x CHbenzene); 100.56 (CHbenzene); 68.07 ((OCH2)2); 65.34 (CH2-benzyl); 31.57 (ω-2); 29.22 (bulk-CH2); 25.71 (B-CH2); 22.59 (ω-1); 14.01 (2x CH3).

3,5-Bis(hexyloxy)-1-(propargyloxy methyl) benzene (16)

15 (5 g, 16.20 mmol) was added slowlyto a suspension of NaH (0.85 g, 21 mmol) in THF at 10 C and stirred for 15min, beforepropargyl bromide (80% w/w in toluene, 3.5 mL 32 mmol) was added dropwise at 10 °C. The reaction mixture was kept stirring for 10 min., before it was allowed to warm to room temperature. Stirring was continued overnight. The reaction mixture was diluted with water and extracted three times with CH2Cl2. The combined organic phases was washed with brine water, dried over MgSO4 and concentrated on a rotary evaporator leaving 16 dark brown oil (5.2 g,93%). 1H NMR (CDCl3) δ= 6.51 (d, 2H, CH-benzene), J= 2.40; 6.41 (t, CH-benzene), J= 2.24; 4.56 (s, CH2-benzyl); 4.18 (d, CH2-propargyl), J=2.4; 3.92 (t, 4H, OCH2); 2.48 (t, CH-propargyl J=2.5 Hz); 1.78 (p, 4H, -CH2); 1.50-1.43 (m, 4H, CH2); 1.37- 1.28 (m, 8H, bulk-CH2); 0.93 (t, 6H, CH3). 13C NMR (CDCl3) δ= 160.43 (2x Cbenzene); 139.41 (Cbenzene); 106.23 (2x CHbenzene); 100.88 (CHbenzene); 79.67 (C-propargyl); 74.57 (CH-propargyl); 71.53 ((OCH2)2); 68.04 (CH2-benzyl); 59.70 (OCH2-propargyl); 31.58 (ω-2); 29.36 (bulk-CH2); 25.73 (B-CH2); 22.60 (ω-1); 14.03 (2x CH3).

NMR Spectra

Surfactant Investigations

Fig. S1: Emulsion stability (O/W).

Fig. S2: Emulsion stability (W/O).

Table S1: Emulsion droplet range size

Surfactants No. / Droplet
Size (µm)
2 / 40-90
4 / 10-50
6 / 8-20
8 / 14-25
9 / 20-65
10 / 4-10

Fig. S3: Emulsion droplet size image under OPM for surfactants A) 2 and B) 4.

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